Of 105 patients enrolled in the single-arm, open-label phase II KEYNOTE-224 study, the objective response rate with pembrolizumab was 16.3% (95% CI, 9.8%-24.9%), with 1 complete response (CR). The median PFS was 4.8 months (95% CI, 3.4-6.6) and the median OS has not been reached. The 6-month PFS and OS rates were 43.1% and 77.9%, respectively. Treatment remained ongoing in 23 patients, reported lead investigator Andrew X. Zhu, MD, PhD.

“With the availability of various options in the treatment of refractory HCC, I think what our data are showing is that single-agent pembrolizumab is showing very impressive antitumor activity as evidenced by the response rate of 16.3%, but also a decent PFS in this population,” said Zhu, Professor of Medicine, Harvard Medical School, and Director, Liver Cancer Research, Massachusetts General Hospital Cancer Center, Boston.

Sorafenib is standard first-line therapy for advanced HCC, with regorafenib (Stivarga) and nivolumab (Opdivo) being the only approved second-line options in selected patients with HCC. Regorafenib was approved based on an improvement in OS in a phase III study while nivolumab was granted an accelerated approval based on response data in a phase I/II study. The phase III KEYNOTE-240 is currently assessing pembrolizumab for pretreated patients with HCC, with a primary endpoint of OS (NCT02702401).

“We think that this agent may become another potential option depending on an ongoing phase III trial,” Zhu said. “If that’s the case, this could be a new agent that we can consider for combination strategies but also looking at biomarkers of response to this class of drugs. More options are good for our patients.” Adding to this, he said that biomarker analysis will be conducted on tissue samples obtained from KEYNOTE-224.

In the phase II study, the efficacy and safety of pembrolizumab monotherapy was assessed in patients with Child Pugh class A advanced HCC who experienced radiographic progression of disease while receiving treatment with sorafenib, or were intolerant to sorafenib, and had a predicted life expectancy >3 months. Of the 105 patients enrolled, 104 were treated with pembrolizumab, 200 mg every 3 weeks for 2 years or until disease progression, unacceptable toxicity, withdrawal of consent, or investigator decision. Response was assessed every 9 weeks per RECIST v1.1 criteria.

Median patient age was 68 years, 21.2% were positive for hepatitis B virus (HBV), and 26.0% were positive for hepatitis C virus (HCV). Some 79.8% discontinued sorafenib for disease progression and 20.2% for intolerance. Extrahepatic disease was present in 63.5%.

In addition to the ORR of 16.3%, the disease control rate was 61.5% (95% CI, 51.5%-70.9%). Best overall response was a partial response in 15.4%, CR in 1.0%, and stable disease in 45.2%. In the responders, the median time to response was 2.1 months. Some 94% of responders were estimated to have a response duration ≥6 months, and the median duration of response was 8.2 months (range, 2.3+ to 8.3+). Responses were observed in patients with HBV or HCV infection and in uninfected patients.

The rate of treatment-related adverse events (TRAEs) of any grade was 73.1%. The most common TRAEs of any grade were pruritus (21.2%), fatigue (12.5%), increased aspartate aminotransferase (9.6%), and diarrhea (9.6%). Overall, 25.0% of patients had grade ≥3 TRAEs and there was 1 treatment-related death from ulcerative esophagitis. There were no flares of HCV or HBV. Immune-mediated hepatitis occurred in 3 patients (2.9%).